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PubMed1978

Effects of cyclophosphamide on the in vivo response of outbred athymic (nude) mice to a thymus-independent antigen (DNP-AGG-Ficoll).

Both nude mice (nu/nu) and their heterozygous littermates (nu/+) were injected with a single IP dose of 300 mg cyclophosphamide (CY)/kg. CY is a known immunosuppressive agent, which affects primarily B lymphocytes. Immunization with the thymus independent antigen DNP-AGG59-Ficoll after CY treatment disclosed that restoration of the primary direct PFC response occurred more rapidly in nude mice than in nu/+ mice. However in these same experiments, the primary indirect PFC response, recovered earlier in nu/+ mice than in nude mice. After CY treatment, secondary indirect PFC responses were delayed in both nude and nu/+ mice, but the greatest effect was seen in nude mice. The data suggest that the presence of T cells has little if any influence on the recovery capacity of those B cells which are destined to become direct PFC. However the recovery of B cells which are destined to produce indirect PFC responses is facilitated by the presence of T cells.

Animals↗
PubMed1986

The relationship between the geniculocortical afferents and their cortical target cells during development of the cat's primary visual cortex.

To study the prenatal development of connections between the lateral geniculate nucleus (LGN) and the primary visual cortex in the cat, we have examined the relationship between the position of ingrowing afferents from the LGN and their target cells in cortical layers 4 and 6 at various times during the cat's 65 d gestation period and during the first 3 weeks of postnatal life. In 1 series of experiments, the method of transneuronal transport of intraocularly injected tritiated proline (3H-proline), followed by autoradiography, was used to label the developing geniculocortical pathway. In another series, the tritiated thymidine (3H-thymidine) method was employed to keep track of the cells destined for layers 4 and 6 by labeling them on their birthdates (layer 4: embryonic day (E) 37-43; layer 6: E31-36) (Luskin and Shatz, 1985b) and then charting their locations at subsequent times during development. The results of the 2 sets of experiments were compared at corresponding ages. By E39, many of the cells of cortical layer 6 have completed their migrations and are situated within the cortical plate immediately above the subplate. However, the transneuronal labeling pattern indicates that the geniculocotical afferents have not yet arrived within the vicinity of the future visual cortex, but rather are still en route and confined within the optic radiations of the telencephalon. By E42, a week after the first afferents can be detected in the radiations, substantial transneuronal label is found in the subplate immediately below future visual cortex. However, the overlying cortical plate is free of label. Over the next 2 weeks, geniculocortical axons continue to accumulate in the subplate zone, and, in addition, transneuronal label can be found in the marginal zone. By E55 a faint geniculocortical projection can be detected within the cortical plate, but only within its deeper half (future layers 5 and 6), and even then the major portion of the projection is still confined to the subplate. The absence of a projection to cortical layer 4 at these ages is remarkable in view of the results from our 3H-thymidine experiments, which indicate that by E57 the majority of cells destined to belong to layer 4 have already completed their migrations and assumed positions superficial to the cells of layers 5 and 6. By birth, a substantial geniculocortical projection to cortical layer 4 can be detected in the transneuronal autoradiographs.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1985

Differential expression of HLA-DR antigens in subsets of human CFU-GM.

Expression of HLA-DR surface antigens by granulocyte/monocyte colony-forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. "Early" (day 14) CFU-GM express higher levels of HLA-DR than do "late" (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high-level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.

Antibodies, Monoclonal↗
PubMed1986

Significance of angiotensin sensitivity test for prediction of pregnancy-induced hypertension.

In 48 normotensive women with epidemiologic high-risk factors for pregnancy-induced hypertension, the angiotensin sensitivity test was performed serially between 26 and 32 weeks of gestation. If an effective pressor dose of less than 12 ng/kg per minute was considered to be a positive test result, 20 subjects were positive at 30 weeks of gestation and destined to develop pregnancy-induced hypertension. Of ten subjects with a false-positive test result, seven patients developed proteinuria and/or clinically significant edema without apparent hypertension, and only three subjects remained normal throughout their pregnancy. Twenty-eight subjects with negative test results had uneventful pregnancies. Before 30 weeks' gestation, it was difficult to identify all patients destined for pregnancy-induced hypertension. Although high false-positive test results were detected, these results suggest that an angiotensin sensitivity test at 30 weeks' gestation represents an appropriate means of identifying women who remain normal throughout pregnancy. Careful follow-up should be undertaken in all patients with positive test results.

Adult↗
PubMed1984

[Epidemiology of travel diarrhea].

Travelers' diarrhea is the most frequent health problem during a stay in developing countries. A recent study basing on interviews with 16,568 charter flight passengers returning to Europe from 13 destinations in various climatic regions provides epidemiological data on a worldwide scale. Significant differences in diarrheal incidence varied not only between individual destinations, but also between hotels in the same area. The highest incidence for a two weeks' stay exceeded 50% in some regions of North and West Africa. Persons under 30 were more often affected than older travelers. Within international groups meeting in developing countries, the risk varied according to the patient's country of origin, with the residents of industrialized nations being most often affected. Even in the tropics, diarrhea usually takes a short and mild course. The various regions show unessential differences in chronology and symptomatology. E. coli is the most frequent causative agent of this ailment.

Adult↗
PubMed1983

Epidemiology of travellers' diarrhoea.

Travellers' diarrhoea is the most frequent health problem encountered during a stay in developing countries. A recent study based on interviews with 16,568 charter-flight passengers returning to Europe from 13 destinations in various climatic regions provides epidemiological data on a worldwide scale. Significant differences in diarrhoeal incidence varied not only between individual destinations, but also between hotels in the same area. Travel characteristics, and a record of former tropical journeys influenced the incidence to a minor degree. Persons under 30 were more often affected than older travellers. Within international groups meeting in developing countries, the risk varied according to the patient's country of origin, with the residents of industrialised nations being most often affected. The various regions show non-essential differences in chronology and symptomatology. This is consistent with quantitative rather than qualitative geographical variations in causative agents. Potentially life-threatening gastrointestinal infections, such as typhoid and cholera, are very rarely acquired by tourists.

Adolescent↗
PubMed1983

Epidemiology of diarrhea in travelers.

To investigate diarrhea in tourists on a worldwide scale, 16,568 passengers were interviewed during their flights home from 13 destinations in various climatic regions. Significant differences in diarrheal incidence were observed between individual destinations and also between hotels in the same area. The highest rates exceeded 50%. Younger persons were more often affected. Sex, travel characteristics, and a record of former tropical journeys influenced the incidence to a minor degree. Even in the tropics, diarrhea usually takes a short (average, 3.6 days) and mild (average of 4.6 stools per day) course. Prophylactic or therapeutic medication only slightly influenced these values. The various regions showed minor differences in chronology and symptomatology. This is consistent with quantitative rather than qualitative geographic variations in causative agents. The traditional nutritional recommendations for prophylaxis seemed to be unrealistic and usually unsuccessful.

Adolescent↗
PubMed1983

Neural pathway constraints in the motor innervation of the chick hindlimb following dorsoventral rotations of distal limb segments.

Several studies have demonstrated that motor axons can discriminate between dorsally and ventrally derived muscles. In this paper we present evidence that (1) the pathway axons take in the limb constrain their access to either dorsally or ventrally derived muscles, and therefore (2) the axon's ability to discriminate between dorsal and ventral is expressed already at the level of pathway selection into the limb. Surgically manipulated hindlimbs were produced consisting of a normal host thigh connected to a dorsoventrally rotated calf or to rotated and duplicated donor limb segments. The limb rotations were done distal to the level at which axons select a dorsally or ventrally destined pathway through the limb, such that at the level of the rotation, axons in each nerve were confronted with the opposite-from-normal set of muscles. In this situation, the relative influence of pathway availability versus dorsal/ventral muscle recognition could be assessed. The innervation of rotated limb segments was, in all cases, opposite from normal. Motoneurons which normally innervate dorsal muscles innervated ventrally derived muscles that had been rotated into a dorsal position. Likewise, normally ventrally destined axons served dorsal muscles in the rotated segments. Thus, motor axons did not alter their distal path to reach their normal set of muscles. While these results do not rule out intrinsic dorsal/ventral differences between muscles, they do demonstrate that muscle surface recognition is not necessary to account for dorsal/ventral discrimination in the innervation of normal, supernumerary, or duplicated limbs, nor is it sufficient to account for the innervation of rotated limb segments. These results also indicate that pathway guidance cues are an important influence on innervation patterns.

Animals↗
PubMedDate not supplied

Interactions between hospital and nursing home use.

National estimates are provided, for the first time, of the number of hospitalizations in a year for elderly persons who also experience some nursing home use, and patterns for this interaction are described. In 1987, 816,000 persons were transferred from nursing homes to hospitals, constituting 8.5 percent of all Medicare hospital admissions for persons ages 65 and older. Another 347,000 hospital stays involved people admitted from the community and discharged to a nursing home. The reporting of discharge destination on Medicare hospital bill data in 1987 also is analyzed. It was found that these data may have underreported a nursing home as the destination by between 15 and 20 percent. The magnitude of hospitalizations of nursing home residents suggests that programs aimed at improving nursing home care might have an important impact on total days of hospital care, and that it is important to learn more about the optimal use of expensive hospital care.

Aged↗
PubMed1995

[What is the future of circumcision?].

Systematic ablation of the prepuce of male children is a sexual mutilation based on the principle of metaphysical sacrifice. It is a painful but partial excision carried out on an organ destined to give pleasure, in order to purchase the right to use what's left. All the other justifications from hygiene to reinforced virility are spurious and have no scientific value. Circumcision is still imposed by African customs and most of monotheistic religions; it is an out-model practice which is destined to vanish as is the Chinese custom of foot-binding of young girls. In the meantime, we can suggest temporary measures which make their mark without mutilation.

Adult↗
PubMedDate not supplied

[Geographical accessibility to health centers and urban planning in Fuenlabrada (Madrid)].

BACKGROUND: The accessibility of care can be inappropriate due to a scarce or nonexistent collaboration between health and urban planners at the time of urban planning. METHODS: The study was carried in the city of Fuenlabrada (145.506 inhabitants), located in the metropolitan area of Madrid. The city is divided in six Basic Zones with a Primary Health Care Center (PHCC) in each one of them. Isometric curves between were drawn on a map between the "starting" and "destination" points (Residential points formed by group of houses and their PHCC, respectively). The average and maximal distances were calculated. A scale to measure geographical accessibility was designed. RESULTS: The 55.646 houses of the city were grouped into 209 "starting points" for the six PHCC ("destination points"). 93 isometric curves were drawn. The average and maximal distances were 910 and 3.900 meters, respectively. The application of our accessibility scale shows that 3 Basic Zones have optimum accessibility, 2 have good accessibility an the last one has bad accessibility. CONCLUSIONS: The accessibility to the PHCC in Fuenlabrada is adequate. If the housing plan continues, in 1995 the city will need a new PHCC and a reorganization of Basic Zones.

City Planning↗
PubMed1995

Development expression of Hox11 and specification of splenic cell fate.

Hox11 is the first member of a novel class of orphan homeobox genes. We report that Hox11 is expressed in a discrete temporal and spatially segmented pattern during embryonic development and appears critical for the specification of splenic cell fate. Expression is first observed in the developing muscle plates of branchial arches 1, 2, 3 and 4/6, and subsequently within motor neurons of cranial nerves V, VII, IX, and X, which innervate these muscles. Hox11 serves as a molecular maker distinguishing branchial from somatic motor nuclei. Additionally, Hox11 is expressed in the surface ectoderm of the first branchial arch in the region destined to become the tongue and teeth and then in ganglia innervating this area. However, Hox11-deficient mice have no apparent morphological of functional defects within these structures. Notably the closely related homeobox genes, Hox11L.1 and Hox1L1.2, were not expressed in a redundant pattern. Neither Hox11L1 nor Hox11L2 was expressed in the branchial arches or their motor nuclei within wild-type or Hox11-/- mice. Beginning at E11.5, Hox11 is normally expressed at a single site in the abdomen within splanchnic mesoderm destined to form the spleen, and Hox11-/- mice have no spleen. We noted no increase in cell death within the dorsal mesogastrium of Hox11-deficient mice. Instead the dorsal mesogastrium fails to separate from the stomach. Hox11-/- mice display a larger stomach and possibly pancreas, suggesting that these mesodermal cells now contribute to other organs.

Animals↗
PubMed1995

The cytogenesis and radial migration of cranial nerve efferent neurons in the developing brain stem of the bovine.

The cytogenesis of motor neurons of the immature brain stem of the bovine has been examined by light-and electron microscopy from the periods of origin and migration of the motor neurons until their transformation into relatively mature neurons in their area of destination. Up to 2.7 cm CRL intensive cell migration occurs from the ventromedial cell column in a ventrolateral direction, leading to the formation of the definitive viscero-efferent nucleus of the facial nerve. Electron-optically these cells exhibit features of immature neurons which are extending leading processes in the direction of their destination. At 2.5 cm CRL a formation of vertical cell columns can be identified in the facial nucleus which has reached its final position. Its perikaryon areas come into contact with radial fibres. This morphological pattern marks the process of migration. An increased ultrastructural differentiation is typical for neurons which are localized in their ultimate position.

Animals↗
PubMed1994

Provocative pharmacologic testing during arterial embolization.

Provocative pharmacologic testing reliably predicts the safety of arterial embolization. Arteries with intra-axial destinations are tested with a barbiturates and arteries with extra-axial destinations are tested with lidocaine. Testing is quickly and easily performed, essentially risk-free, and reduces the incidence of complications. Despite extensive knowledge of microvascular anatomy, anatomic variations and branches below the limits of angiographic resolution make provocative pharmacologic testing essential to minimize complications during arterial embolization.

Adolescent↗
PubMed1996

Effects of cerebellar lesions on saccade simulations.

Experimental studies involving cerebellar lesions have been important tools for learning about the operation of the saccadic eye movement system. These studies have been used to further develop a neural network model for horizontal saccadic eye movement control. The neural control mechanism is first order time optimal, initiated by the deep layers of the superior colliculus and terminated by the cerebellar fastigial nucleus. The neural circuit consists of neurons in the paramedian pontine reticular formation (burst, tonic and pause cells), the vestibular nucleus, abducens nucleus, oculomotor nucleus, cerebellum, substantia nigra, nucleus reticularis tegmenti pontis, the thalamus, the deep layers of the superior colliculus and the oculomotor plant for each eye. Agonist burst cell activity is initiated with maximal firing due to an error between the target and eye position, and continues until the internal eye position in the cerebellar vermis reaches the desired position, then decays to zero. The cerebellar vermis is responsible for adapting the duration of maximal firing based on the initial position of the eye. There are two sets of neural integrators in the neural network. One operates within the cerebellar vermis to predict the width of the pulse, and the other within the paramedian pontine reticular formation to maintain the eyes at their destination. Antagonist neural activity is inhibited during the agonist burst activity. After the agonist burst, antagonist neural activity rises with a stochastic rebound burst and from input from the fastigial nucleus, then falls to a tonic firing level necessary to keep the eye at its destination. The onset of the antagonist tonic firing is stochastic, weakly coordinated with the end of the agonist burst, and under cerebellar control. A common mechanism of action is described, based on cerebellar gating, through the fastigial nucleus, that explains a number of different saccadic eye movement types, including dynamic overshoot, glissadic overshoot and undershoot, and undershoot. A linear homeomorphic oculomotor muscle model is used in the simulations of the operation of the neural network. Each of the neural sites in the model fire similar to experimental data, and simulate fast eye movements.

Cerebellum↗
PubMed1996

Gonadal cell apoptosis.

Apoptosis is an important cellular process by which superfluous or unwanted cells are deleted from an organism during tissue remodeling and differentiation. Recent studies have demonstrated the role of this programmed cell death or "controlled cell suicide" in the physiological function of an organism. Suppression of apoptosis increases the susceptibility of an individual to malignancy whereas uncontrolled cell death is associated with degenerative diseases. Normal development of both female and male gonads is characterized by massive cell death. More than 99% of ovarian follicles endowed at early life are destined to undergo apoptosis and the exhaustion of these follicles serves as a "clock" for female reproductive senescence. In the testis, up to 75% of male germ cells also undergo apoptosis, perhaps as a mechanism to delete superfluous or defective germ cells. Gonadal cell apoptosis provides valuable models to study hormonal regulation of apoptosis. In the ovary, gonadotropins, estrogens, growth hormone, growth factors (IGFI, EGF/TGF-alpha, basic FGF), cytokine (interleukin-1 beta) and nitric oxide act in concert to ensure the survival of preovulatory follicles. In contrast, androgens, interleukin-6 and gonadal GnRH-like peptide are apoptotic factors. Developmental studies further indicate that fractions of endowed follicles are recruited throughout the reproductive life whereas most of the primordial follicles are "arrested" at the initial stage of development for a prolonged time. Because a transcriptional factor WT1 is expressed in high levels in follicles at early stages of development and because WT1 over-expression represses the promoter activity of inhibin-alpha gene, this nuclear protein may be important in the maintenance of follicles at early stages of development. Once a cohort of follicles is recruited to grow, it is destined to undergo apoptosis unless rescued by survival factors. After puberty onset and under gonadotropin stimulation, some of the growing antral follicles are "selected" to continue their final maturation and secrete high levels of estrogens to trigger ovulation. Following repeated cycles of recruitment, atresia or ovulation, the follicle reserve is exhausted, thus signaling the onset of reproductive senescence. Although the somatic granulosa cell is the major cell type undergoing apoptosis in the ovary, the germ cells in the testis also exhibit signs of apoptotic cell demise. In the testis, gonadotropins and androgens act as survival factors whereas exposure to elevated temperature in cryptorchid testes increases apoptosis. In the seasonally breeding hamster model, photoperiod-entrained regression and recrudescence of testis tissue serves as a unique natural model of apoptosis. With recent advances in our understanding of the cellular mechanism of apoptosis, including the elucidation of the Ced9/bc12 and Ced3/ICE family of proteins, further investigation of gonadal apoptosis may lead to a better understanding of gonadal degenerative disorders (such as premature ovarian failure and oligospermia), reproductive senescence and tumorigenesis. The gonadal model should also be valuable in studying the regulation of intracellular apoptosis genes by external hormonal signals.

Animals↗
PubMed1996

[Experimental and pathological models that explain the regulation of cellular migration and axon's orientations].

Since Cajal discovery of nerve growth cones and their role in the growth, metabolism and destination of the axon in 1890 numerous studies have corroborated with more sophisticated techniques his original findings and ideas. The use of modified Golgi staining, drawing from the camera lucida in 2 combination with electron microscopy and t retrograde biochemical markers have helped to identify the neuronal sites of synapsis. Dynamic studies of the nerve growth cones using time-lapsed video microscopic images of living neuroblast in t culture or the intact animal have demonstrated their protactil and retractile membranes and exploratory filipodia properties. Interaction between growth cone membrane receptors and different molecules along the migrating axon determine also its final destination. Finally the role that genes play on neuronal migration and in guiding the axons to reach their targets have been identified in patients with Kallmann syndrome, a migrational disorder of olfactory axons and hypothalamic gonadotropic hormone-releasing hormone with absent gene at Xp22.3 locus manifested by anosmia and hypogonadotropic hypogonadism.

Axons↗
PubMed1996

Dynamics of mismatch correction in the hippocampal ensemble code for space: interaction between path integration and environmental cues.

Populations of hippocampal neurons were recorded simultaneously in rats shuttling on a track between a fixed reward site at one end and a movable reward site, mounted in a sliding box, at the opposite end. While the rat ran toward the fixed site, the box was moved. The rat returned to the box in its new position. On the initial part of all journeys, cells fired at fixed distances from the origin, whereas on the final part, cells fired at fixed distances from the destination. Thus, on outward journeys from the box, with the box behind the rat, the position representation must have been updated by path integration. Farther along the journey, the place field map became aligned on the basis of external stimuli. The spatial representation was quantified in terms of population vectors. During shortened journeys, the vector shifted from an alignment with the origin to an alignment with the destination. The dynamics depended on the degree of mismatch with respect to the full-length journey. For small mismatches, the vector moved smoothly through intervening coordinates until the mismatch was corrected. For large mismatches, it jumped abruptly to the new coordinate. Thus, when mismatches occur, path integration and external cues interact competitively to control place-cell firing. When the same box was used in a different environment, it controlled the alignment of a different set of place cells. These data suggest that although map alignment can be controlled by landmarks, hippocampal neurons do not explicitly represent objects or events.

Animals↗